Ergothioneine, shown in Formula 1, was originally described as a component of ergot fungus (Eagles, B. A., J. Am. Chem. Soc'y (1928) 50 pp. 1386-87) which did not possess ergot alkaloid activity. This compound was identical with a thiol previously known to occur in human and animal blood (see for example Eagles, B. A. and Johnson, T. B., J. Am. Chem. Soc'y 49 (1927) pp. 575-80). Ergothioneine was early recognized to be present in normal human blood in both health and disease (Touster, O. and M. C. Yarbro, J. Lab. & Clinical Med. 39(5) (1952) pp. 720-24), and was found to reside exclusively in the erythrocytes (Rae, C. D. et al., Magnetic Resonance in Med. 29(6) (1993) pp. 826-29). Ergothioneine was found to be present even in the central nervous system (Briggs, I., J. of Neurochem. 19(1) (1972) pp. 27-35) and at especially high levels in seminal fluid (Mann, T. and E. Leone, Biochem. J. 53(1) (1953) pp. 140-8), and also in the cornea (Shires, T. K. et al., Toxicology, Endocrinology 117(1) (1997) pp. 117-20).
Interestingly, ergothioneine is biosynthesized exclusively by fungi and mycobacteria. In plants, ergothioneine is assimilated by the roots after fungal synthesis inside the conidia. In man, it is assimilated solely through food. Ergothioneine is specifically taken up in the erythrocytes by a specific transporter (Gründemann, D. et al., Proceedings Nat'l Acad. Sci. of U.S. 102(14) (2005) pp. 5256-61) and remains in them for a long period, thus giving ergothioneine a long biological half-life (Wolf, G. et al., Biochimica et Biophysica Acta 54 (1961) pp. 287-93).
Although there has been recent controversy as to the precise role of ergothioneine in the human and animal body (Brummel, M. C., Med. Hypotheses 18(4) (1985) pp. 351-70), it was hypothesized and subsequently demonstrated in a wide variety of in vivo and in vitro models that the compound possesses potent antioxidant properties (Akanmu, D., et al., Archives of Biochem. & Biophysics, 288(1) (1991) pp. 10-16; Arduini, A. et al., Archives of Biochem. & Biophysics 281(1) (1990) pp. 41-3; Aruoma, O. I. et al., Food & Chem. Toxicology 37(11) (1999) pp. 1043-53; Bedirli, A., et al., J. Surgical Research 122 (2004) pp. 96-102; Hartman, P. E., Methods in Enzymology 186 (1990) pp. 310-18.; Hartman, Z. and Hartman, P. E., Envtl. & Molecular Mutagenesis 10 (1987) pp. 3-15.; Jang, J. H. et al., Free Radical Biology & Med. 36 (2004) pp. 288-99.; Moncaster, J. A. et al., Neuroscience Letters 328 (2004) pp. 55-59.; Obayashi, K. et al., J. Cosmetic Sci. 56 (2005) pp. 17-27; and references therein which are incorporated herein by reference). Free radicals derived from endogenous and exogenous thiol (sulphur)-containing compounds are involved in a number of important biological processes, such as the protection of living systems subjected to ionizing radiation or other sources of free-radical damage. Thiol or thione functions can be associated with the imidazole ring leading to the mercaptoimidazole ergothioneine(I), which exerts chemoprotection against oxidative stress and carcinogenesis.
Dietary ergothioneine, a compound of plant origin, is assimilated and conserved by mammals (see references supra). In aqueous solution, ergothioneine has a predominantly thione rather than tautomeric thiol structure. It is considered to be a natural chemoprotector against oxidation including lipid peroxidation. Ergothioneine deactivates singlet oxygen at a higher rate constant than is observed for simple thiols, including glutathione. It diminishes the mutagenicity of cumene and t-butylhydroperoxides in Salmonella bacteria (see references supra).